The only certain cure of cancer is the complete removal of the malignant tissue by surgery. A complete removal would prevent the re-growth of the tumor and eliminate the need for a second operation. One of the difficulties during the operation is to determine if all of the cancerous tissue has been removed from the tumor margin. Currently surgeons rely on visual inspection of the surgical cavity and random tissue sampling of the margins, or pathology results on the excised tissue that is often ready after the surgery is concluded. Radiolabeled tumor markers have preferentially high uptake in cancerous cells and offer a unique opportunity for detection of occult tumors at the margin. Background: Beta rays have a range of a few millimeters in tissue. Beta ray detectors, in conjunction with beta emitting isotopes are ideal for detection of occult tumors on the margin since background radiation would not interfere with identification of margins. Previously we have developed a beta probe and beta camera detector and demonstrated that they are selectively sensitive to beta rays. An instrument with imaging capability would further aid the surgeon to quickly and accurately localize any positive tumor margins. Beta cameras have been proposed in the past, but have never been used clinically, because of problems designing a camera that is sensitive and at the same time electrically safe to use during surgeries. Novelty: In this submission, we are proposing a novel beta-camera design based on the use of Solid State Photomultipliers (SSPMs). SSPMs is a relatively new class of photo-sensors that have been shown to have a performance close to that of conventional PMTs, but only requiring operating at tens of volts instead of kV needed for PMTs. Thus, the use of SSPM would significantly alleviate the electrical safety aspect of using the beta-camera intra-operatively. Multiple detector modules will also be tested to increase sensitivity to beta and decrease sensitivity for gamma rays. Preliminary Studies: Recently we performed a pilot study that involved 7 patients that underwent lumpectomy. During the procedure, the surgical cavity and excised tissues were surveyed with a beta-probe. We found that the background in the surgical cavity detected by the beta-probe was only a 12 18 cps, while a 5 mg generated 3518 cps, showing that the gamma background is low enough to allow detection of uptake in small volumes of tissues. Another conclusion from this study was that an imaging device is needed to allow a more rapid and accurate survey of the surgical cavity. We have built a prototype of the SSPM-based beta camera in an small scale and demonstrated its feasibility. Research Plan (Phase I): We will build the camera with a sheet of plastic scintillator and a 5x5 array of new ceramic-mounted SSPMs. We will experiment with Peltier coolers to lower the temperature of the SSPM array. We will optimize the sensitivity of the camera, and perform characterization, and limit of detection tests with phantoms. We will test the novel concept of coincidence discrimination to reduce the electronic noise of SSPMs and increase the sensitivity of the camera to low energy beta rays. We will test a dual detector module design to reduce the background gamma sensitivity. We will test a module for the camera with one layer of SSPMs and 2 layers of different scintillators that are differentiated by decay-time constants and phoswitch circuitry. R&D and Clinical Trials Plan (Phase II): The best detector module concept will be selected for building a beta camera for clinical trial. The electronics, mechanical housing, and software for the camera, as well as a Laparoscopic version of the camera will be built and tested during the first part of the Phase II. The prototypes of these cameras will be designed to pass electrical and environmental standards of surgical instruments, and will be sent to CSA in order to obtain UL safety certificates. We will submit a New Device Exemption (NDE) application to FDA for testing the cameras in breast and prostate. During the later part of Phase II we will conduct clinical trials with our long term collaborator Dr. Armando Giuliano on detection of margins in lumpectomy using FDG. Thirty patients will enroll is this study and the existing IRB protocol for beta probe will be amended to include beta camera. Together with Drs. Bander and Tewari at Cornell we will test the laparoscopic beta camera in robotic prostatectomies, in conjunction with a monoclonal antibody, called J591, against PSMA that is labeled with Lu-177 (a beta emitter). The on going IRB approved studies of Lu-177-J591 Mab will be amended to include beta camera exploration laparoscopically. Statistical Analysis: Both studies are designed to determine the efficacy, sensitivity, and specificity of the beta cameras in detection of tumors on the margins of resection. The ROC analysis of the beta camera with visual detection of the surgeons will show if beta cameras added can help increase the rate of margin detection.